JPH07138206A - Production of o, o'-diacyltartaric acid - Google Patents
Production of o, o'-diacyltartaric acidInfo
- Publication number
- JPH07138206A JPH07138206A JP31453093A JP31453093A JPH07138206A JP H07138206 A JPH07138206 A JP H07138206A JP 31453093 A JP31453093 A JP 31453093A JP 31453093 A JP31453093 A JP 31453093A JP H07138206 A JPH07138206 A JP H07138206A
- Authority
- JP
- Japan
- Prior art keywords
- water
- crystals
- formula
- organic solvent
- diacyltartaric
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、各種ラセミアミン類の
光学分割剤として有用な光学活性Ｏ，Ｏ´−ジアシル酒
石酸の製造方法に関するものである。FIELD OF THE INVENTION The present invention relates to a method for producing optically active O, O'-diacyltartaric acid useful as an optical resolving agent for various racemic amines.
【０００２】[0002]
【従来の技術】従来、Ｏ，Ｏ´−ジアシル酒石酸の代表
例である、Ｏ，Ｏ´−ジベンゾイル酒石酸の製造方法に
は、（１）Ｏ，Ｏ´−ジベンゾイル酒石酸無水物を水中
で加熱して加水分解させたのち、冷却してＯ，Ｏ´−ジ
ベンゾイル酒石酸の結晶を得る方法（Ｊ．Ａｍ．Ｃｈｅ
ｍ．Ｓｏｃ．，５５，２６０５（１９３３））、（２）
Ｏ，Ｏ´−ジベンゾイル酒石酸無水物を水とジクロロメ
タンの混合溶媒中で、１．５〜５ａｔｍの加圧下で、加
熱して加水分解させたのち、冷却してＯ，Ｏ´−ジベン
ゾイル酒石酸の結晶を得る方法（ＨＵ２２１４７）など
が提案されている。2. Description of the Related Art A conventional method for producing O, O'-dibenzoyltartaric acid, which is a typical example of O, O'-diacyltartaric acid, comprises (1) heating O, O'-dibenzoyltartaric anhydride in water. And hydrolyzed, followed by cooling to obtain crystals of O, O'-dibenzoyltartaric acid (J. Am. Che.
m. Soc. , 55, 2605 (1933)), (2)
O, O'-dibenzoyltartaric acid anhydride was heated and hydrolyzed in a mixed solvent of water and dichloromethane under a pressure of 1.5 to 5 atm, and then cooled to obtain crystals of O, O'-dibenzoyltartaric acid. Has been proposed (HU22147) and the like.
【０００３】[0003]
（１）法においては、Ｏ，Ｏ´−ジベンゾイル酒石酸無
水物を加水分解すると、生成したＯ，Ｏ´−ジベンゾイ
ル酒石酸が油状物として分離してくる。この油状物が結
晶化する際、結晶が凝集した塊状物ができ、またその結
晶が装置の壁および撹拌機等に付着して反応装置から取
り出すことができなくなるなど操作性が悪く、工業的な
製造法には適さない。（２）法においては、操作性は良
いものの有害なジクロロメタンを大量に使用し、また１
回の操作での収率も低いので好ましい方法とはいい難
い。In the method (1), when O, O′-dibenzoyltartaric acid anhydride is hydrolyzed, the produced O, O′-dibenzoyltartaric acid separates as an oily substance. When this oily substance crystallizes, agglomerates of crystals are formed, and the crystals adhere to the walls of the apparatus, stirrers, etc., and cannot be taken out from the reaction apparatus. Not suitable for manufacturing method. In the method (2), a large amount of harmful dichloromethane is used although the operability is good.
It is difficult to say that this is a preferable method because the yield in a single operation is low.
【０００４】従って、本発明の目的は、塊状物を生成す
ることなく、操作性良く、高収率でＯ，Ｏ´−アシル酒
石酸の結晶を得る方法を提供することである。Therefore, an object of the present invention is to provide a method of obtaining crystals of O, O'-acyl tartaric acid with good operability and in high yield, without forming lumps.
【０００５】本発明者らは、操作性が良好で、かつ収率
が高い方法について鋭意研究した結果、Ｏ，Ｏ´−ジア
シル酒石酸無水物が加水分解して生成したＯ，Ｏ´−ジ
アシル酒石酸と水との混合物に水と混和しない有機溶媒
を共存させることにより、上記目的を達成することがで
きる方法を見出し、本発明を完成するに至った。As a result of earnest studies on a method having good operability and high yield, the present inventors have found that O, O'-diacyltartaric acid anhydride is hydrolyzed to form O, O'-diacyltartaric acid. The present invention has been completed by finding a method capable of achieving the above object by allowing an organic solvent immiscible with water to coexist in a mixture of water and water.
【０００６】すなわち、本発明は、下記一般式（Ｉ）That is, the present invention provides the following general formula (I)
【化１】 （式中Ｒ1 、Ｒ2 は水素原子，ハロゲン原子或いは炭素
数１〜３のアルキル基を示し、Ｒ1 、Ｒ2 が同一でも、
異なっても良い。）で示される化合物を水中で加水分解
して下記一般式（II）[Chemical 1] (In the formula, R 1 and R 2 represent a hydrogen atom, a halogen atom or an alkyl group having 1 to 3 carbon atoms, and even if R 1 and R 2 are the same,
It can be different. ) Is hydrolyzed in water to give a compound represented by the following general formula (II)
【化２】 （式中Ｒ1 、Ｒ2 は一般式（Ｉ）のＲ1 、Ｒ2 と同じも
のであり、水素原子、ハロゲン原子或いは炭素数１〜３
のアルキル基を示す。）で示される化合物を得るに際
し、水と混和しない有機溶媒を共存させることを特徴と
する一般式（II）で示されるＯ，Ｏ´−ジアシル酒石酸
の製造方法を提供する。[Chemical 2] (Are those same as R 1, R 2 in the formula R 1, R 2 is the formula (I), a hydrogen atom, a halogen atom or 1 to 3 carbon atoms
Is an alkyl group. The method for producing O, O′-diacyltartaric acid represented by the general formula (II) is characterized by allowing an organic solvent immiscible with water to coexist when obtaining the compound represented by the formula (1).
【０００７】以下、本発明を詳細に説明する。The present invention will be described in detail below.
【０００８】本発明の原料となるＯ，Ｏ´−ジアシル酒
石酸無水物は周知の化合物であり、広く知られた通常の
方法で製造することができる。The O, O'-diacyltartaric anhydride, which is a raw material of the present invention, is a well-known compound and can be produced by a widely known ordinary method.
【０００９】本発明の方法に特有な、水と混和しない有
機溶媒とは、２０〜９０℃における水への溶解度が２％
以下のものであり、そのような有機溶媒としては次のよ
うなものが挙げられる。例えばベンゼン、トルエン、キ
シレンのような芳香族炭化水素化合物、ヘキサン、オク
タンのような脂肪族炭化水素化合物、１，２−ジクロロ
エタン、１，１，２−トリクロロエタン、クロロベンゼ
ンのような塩素化炭化水素化合物であり、中でもベンゼ
ン，トルエン、キシレン、クロロベンゼンが好ましい。
なお、２種以上の溶媒を併用することも可能である。添
加する有機溶媒の量はＯ，Ｏ´−ジアシル酒石酸無水物
に対して通常０．０１乃至０．５倍重量、好ましくは
０．０３乃至０．２倍重量である。この範囲よりも有機
溶媒の量が少ないと塊状物の生成防止効果が不十分であ
り、この範囲よりも多いと経済的に好ましくない。The water-immiscible organic solvent peculiar to the method of the present invention has a solubility in water at 20 to 90 ° C. of 2%.
The following are mentioned and examples of such an organic solvent include the following. For example, aromatic hydrocarbon compounds such as benzene, toluene and xylene, aliphatic hydrocarbon compounds such as hexane and octane, chlorinated hydrocarbon compounds such as 1,2-dichloroethane, 1,1,2-trichloroethane and chlorobenzene. Among them, benzene, toluene, xylene and chlorobenzene are preferable.
It is also possible to use two or more solvents in combination. The amount of the organic solvent added is usually 0.01 to 0.5 times by weight, preferably 0.03 to 0.2 times by weight, of the O, O′-diacyl tartaric anhydride. If the amount of the organic solvent is less than this range, the effect of preventing the formation of agglomerates is insufficient, and if it is more than this range, it is economically unfavorable.
【００１０】Ｏ，Ｏ´−ジアシル酒石酸無水物を加熱し
て加水分解する際に添加する水の量は、Ｏ，Ｏ´−ジア
シル酒石酸無水物に対して等モル量以上であればよい
が、加水分解を行った後のＯ，Ｏ´−ジアシル酒石酸の
油状物を結晶化させる際に良好な操作性を保つために
は、添加する水の量はＯ，Ｏ´−ジアシル酒石酸無水物
に対して通常０．５乃至１０倍重量、好ましくは１．５
乃至５倍重量である。これより水の量が少ないと、油状
物を結晶化した後のスラリー濃度が高すぎて、攪拌が困
難になるので好ましくない。The amount of water added when the O, O'-diacyl tartaric acid anhydride is heated and hydrolyzed may be at least an equimolar amount with respect to the O, O'-diacyl tartaric acid anhydride. In order to maintain good operability in crystallizing the oily product of O, O′-diacyltartaric acid after hydrolysis, the amount of water added is based on O, O′-diacyltartaric anhydride. Usually 0.5 to 10 times, preferably 1.5
To 5 times the weight. If the amount of water is less than this, the concentration of the slurry after crystallization of the oily substance is too high and stirring becomes difficult, which is not preferable.
【００１１】一般的な加水分解の方法としては、例えば
Ｏ，Ｏ´−ジアシル酒石酸無水物と水とを７０乃至１０
０℃に加熱する。反応時間は化合物により異なるが、通
常０．５〜５時間で終了する。圧力は常圧、加圧のいず
れも採用できる。上記水と混和しない有機溶媒を添加す
る時機は、Ｏ，Ｏ´−ジアシル酒石酸無水物を水中で加
熱して加水分解する前でもよく、また加水分解の途中或
いは加水分解終了後のＯ，Ｏ´−ジアシル酒石酸が油状
化している時でもよい。As a general hydrolysis method, for example, O, O'-diacyl tartaric anhydride and water are mixed in an amount of 70 to 10
Heat to 0 ° C. Although the reaction time varies depending on the compound, it is usually completed in 0.5 to 5 hours. The pressure can be either normal pressure or increased pressure. The time for adding the water-immiscible organic solvent may be before heating the O, O′-diacyl tartaric anhydride in water to hydrolyze it, or during the hydrolysis or after completion of hydrolysis, O, O ′. -Also possible when diacyl tartaric acid is oiled.
【００１２】このようにして加水分解したＯ，Ｏ´−ジ
アシル酒石酸の結晶は、加水分解を行った後のＯ，Ｏ´
−ジアシル酒石酸の油状物を含む反応混合物を徐々に冷
却することによって取得することができる。更に、本発
明を効果的に実施するには種晶を添加する方法が好まし
い。加水分解するとＯ，Ｏ´−ジアシル酒石酸の油状物
が反応系から分離してくるが、この油状物が結晶化する
温度は、加えた有機溶媒の量或いは化合物の種類によっ
て若干変動する。操作性が良好で、粒径の揃った結晶を
得るためには、例えばＯ，Ｏ´−ジ−ｐ−トルオイル酒
石酸の場合は、通常６３℃付近でＯ，Ｏ´−ジ−ｐ−ト
ルオイル酒石酸の種晶を加えて徐々に冷却し、結晶化が
始まったならばその温度を維持したまま攪拌を続けて油
状物を完全に結晶化させればよい。またＯ，Ｏ´−ジベ
ンゾイル酒石酸の場合は、通常５５℃付近でＯ，Ｏ´−
ジベンゾイル酒石酸の種晶を加えて徐々に冷却し、結晶
化が始まったならばその温度を維持したまま攪拌を続け
て油状物を完全に結晶化させる。この時結晶化が始まる
前に加えた種晶が油状化したならば、再度種晶を添加し
て結晶化が始まるのを待てば、同様の効果が得られる。The crystals of O, O'-diacyltartaric acid hydrolyzed in this manner are O, O 'after hydrolysis.
It can be obtained by gradual cooling of the reaction mixture containing the oil of diacyl tartaric acid. Further, a method of adding a seed crystal is preferable in order to effectively carry out the present invention. When hydrolyzed, an O, O'-diacyltartaric acid oil is separated from the reaction system, but the temperature at which this oil crystallizes varies slightly depending on the amount of organic solvent added or the type of compound. In order to obtain crystals with good operability and uniform particle size, for example, in the case of O, O′-di-p-toluoyl tartaric acid, O, O′-di-p-toluoyl tartaric acid is usually added at around 63 ° C. The seed crystals of (1) are added and the mixture is gradually cooled, and when crystallization starts, the oily matter may be completely crystallized by continuing stirring while maintaining the temperature. In the case of O, O'-dibenzoyltartaric acid, O, O'-is usually around 55 ° C.
Seed crystals of dibenzoyltartaric acid are added and the mixture is gradually cooled, and when crystallization starts, stirring is continued while maintaining the temperature to completely crystallize the oily substance. At this time, if the seed crystals added before the start of crystallization become oily, the same effect can be obtained by adding the seed crystals again and waiting for the start of crystallization.
【００１３】このようにして得られた反応スラリ−は室
温まで冷却したのち結晶を濾別すればよい。The reaction slurry thus obtained may be cooled to room temperature and then the crystals may be filtered off.
【００１４】本発明の方法によれば、結晶化の際にＯ，
Ｏ´−ジアシル酒石酸水和物が反応装置の壁或いは撹拌
機等に付着して反応装置から取り出すことができなくな
るなどのトラブルが発生することなく、高収率で操作性
良くＯ，Ｏ´−ジアシル酒石酸を製造することができ
る。According to the method of the present invention, O,
O′-diacyl tartaric acid hydrate does not cause troubles such that the O′-diacyl tartaric acid hydrate adheres to the wall of the reactor or a stirrer and cannot be taken out from the reactor, and the O, O′- Diacyl tartaric acid can be produced.
【００１５】[0015]
【実施例】以下、実施例により本発明をするが、本発明
はこれらの実施例により限定されるものではない。The present invention will be described below with reference to examples, but the present invention is not limited to these examples.
【００１６】比較例１ 攪拌機、温度計、およびコンデンサーを装着した３００
ｍｌの反応器にジ−ｐ−トルオイル−Ｌ−酒石酸無水物
５０ｇと水１５０ｇを入れ、９０〜９５℃で１時間攪拌
して加水分解させた。反応液を７５℃まで冷却してジ−
ｐ−トルオイル−Ｌ−酒石酸の種晶０．１ｇを加えたの
ち徐々に冷却した。７３℃に於いて油状物が結晶化し始
めたのでその温度を維持したまま１時間攪拌を続けた。
結晶化が完全に終了したのち反応スラリ−を室温まで冷
却し、結晶を濾別した。得られたケ−クを乾燥して白色
結晶のＯ，Ｏ´−ジ−ｐ−トルオイル−Ｌ−酒石酸水和
物３２．３ｇを得た。結晶水をカ−ルフィッシャ−法で
測定したところ４．９％であった。（収率５８．６
％）。得られた結晶を２０メッシュの篩で振るったとこ
ろその４８％が篩をパスした。また反応装置の壁および
撹拌機等に付着して反応装置から取り出すことができな
かった結晶の量は２０．９ｇであり、全結晶量の３９．
３％であった。 Comparative Example 1 300 equipped with a stirrer, a thermometer, and a condenser
50 ml of di-p-toluoyl-L-tartaric acid anhydride and 150 g of water were put into a reactor of ml, and hydrolyzed by stirring at 90 to 95 ° C for 1 hour. Cool the reaction mixture to 75 ° C and
After 0.1 g of seed crystals of p-toluoyl-L-tartaric acid was added, the mixture was gradually cooled. At 73 ° C., an oily substance began to crystallize, so stirring was continued for 1 hour while maintaining the temperature.
After the crystallization was completely completed, the reaction slurry was cooled to room temperature and the crystals were separated by filtration. The cake obtained was dried to obtain 32.3 g of O, O'-di-p-toluoyl-L-tartaric acid hydrate as white crystals. It was 4.9% when the water of crystallization was measured by the Cal-Fisher method. (Yield 58.6
%). When the obtained crystals were shaken with a 20-mesh sieve, 48% thereof passed through the sieve. The amount of crystals that could not be taken out from the reaction device by adhering to the wall of the reaction device and the stirrer was 20.9 g, which was 39.
It was 3%.
【００１７】比較例２ 比較例１の反応器にジベンゾイル−Ｄ−酒石酸無水物５
０ｇと水１５０ｇを入れ、９０〜９５℃で１時間攪拌し
て加水分解させた。反応液を５５℃まで冷却してジベン
ゾイル−Ｄ−酒石酸の種晶０．１ｇを加えたのち徐々に
冷却した。５３℃に於いて油状物が結晶化し始めたので
その温度を維持したまま１時間攪拌を続けた。結晶化が
完全に終了したのち反応スラリ−を室温まで冷却し、結
晶を濾別した。得られたケ−クを乾燥して白色結晶の
Ｏ，Ｏ´−ジベンゾイル−Ｄ−酒石酸水和物２８．４ｇ
を得た。結晶水をカ−ルフィッシャ−法で測定したとこ
ろ４．７％であった。（収率５１．４％）。得られた結
晶を２０メッシュの篩で振るったところその４１％が篩
をパスした。また反応装置の壁および撹拌機等に付着し
て反応装置から取り出すことができなかった結晶の量は
２３．５ｇであり、全結晶量の４５．３％であった。 Comparative Example 2 Dibenzoyl-D-tartaric anhydride 5 was added to the reactor of Comparative Example 1.
0 g and 150 g of water were added, and the mixture was stirred at 90 to 95 ° C for 1 hour for hydrolysis. The reaction solution was cooled to 55 ° C., 0.1 g of seed crystals of dibenzoyl-D-tartaric acid were added, and then cooled gradually. At 53 ° C., an oily substance began to crystallize, so stirring was continued for 1 hour while maintaining the temperature. After the crystallization was completely completed, the reaction slurry was cooled to room temperature and the crystals were separated by filtration. The cake thus obtained was dried to give 28.4 g of O, O'-dibenzoyl-D-tartaric acid hydrate as white crystals.
Got It was 4.7% when the water of crystallization was measured by the Karl Fisher method. (Yield 51.4%). When the obtained crystals were shaken with a 20-mesh sieve, 41% thereof passed through the sieve. The amount of crystals attached to the wall of the reactor and the stirrer and the like could not be taken out from the reactor was 23.5 g, which was 45.3% of the total amount of crystals.
【００１８】実施例１ 攪拌機、温度計、およびコンデンサーを装着した３００
ｍｌの反応器にＯ，Ｏ´−ジ−ｐ−トルオイル−Ｌ−酒
石酸無水物５０ｇと水１５０ｇを入れ、９０〜９５℃で
１時間攪拌して加水分解させた。反応液を６３℃まで冷
却してトルエン５ｇとＯ，Ｏ´−ジ−ｐ−トルオイル−
Ｌ−酒石酸の種晶０．１ｇを加えたのち徐々に冷却し
た。６１℃に於いて油状物が結晶化し始めたのでその温
度を維持したまま１時間攪拌を続けた。結晶化が完全に
終了したのち反応スラリ−を室温まで冷却し、結晶を濾
別した。得られたケ−クを乾燥して白色結晶のＯ，Ｏ´
−ジ−ｐ−トルオイル−Ｌ−酒石酸水和物５２．７ｇを
得た。結晶水をカ−ルフィッシャ−法で測定したところ
４．３％であった。（収率９６．２％）。得られた結晶
を２０メッシュの篩で振るったところその９８％が篩を
パスした。また反応装置の壁および撹拌機等に付着して
反応装置から取り出すことができなかった結晶の量は
０．８ｇであり、全結晶量の１．５％であった。 Example 1 300 equipped with a stirrer, thermometer, and condenser
50 ml of O, O'-di-p-toluoyl-L-tartaric acid anhydride and 150 g of water were placed in a ml reactor and stirred at 90 to 95 ° C for 1 hour for hydrolysis. The reaction solution was cooled to 63 ° C., and 5 g of toluene and O, O′-di-p-toluoyl-
After adding 0.1 g of L-tartaric acid seed crystals, the mixture was gradually cooled. At 61 ° C., an oily substance began to crystallize, so stirring was continued for 1 hour while maintaining the temperature. After the crystallization was completely completed, the reaction slurry was cooled to room temperature and the crystals were separated by filtration. The cake obtained was dried to give white crystals of O and O '.
52.7 g of di-p-toluoyl-L-tartaric acid hydrate was obtained. It was 4.3% when the water of crystallization was measured by the Karl Fischer method. (Yield 96.2%). When the obtained crystals were shaken with a 20-mesh sieve, 98% thereof passed through the sieve. The amount of crystals that could not be taken out from the reaction device by adhering to the walls of the reaction device and the stirrer was 0.8 g, which was 1.5% of the total amount of crystals.
【００１９】実施例２ 実施例１の反応器にＯ，Ｏ´−ジベンゾイル−Ｄ−酒石
酸無水物５０ｇと水１５０ｇを入れ、９０〜９５℃で１
時間攪拌して加水分解させた。反応液を５０℃まで冷却
してトルエン５ｇとＯ，Ｏ´−ジベンゾイル−Ｄ−酒石
酸の種晶０．１ｇを加えたのち徐々に冷却した。４８℃
に於いて油状物が結晶化し始めたのでその温度を維持し
たまま１時間攪拌を続けた。結晶化が完全に終了したの
ち反応スラリ−を室温まで冷却し、結晶を濾別した。得
られたケ−クを乾燥して白色結晶のＯ，Ｏ´−ジベンゾ
イルル−Ｄ−酒石酸水和物５１．２ｇを得た。結晶水を
カ−ルフィッシャ−法で測定したところ４．６％であっ
た。（収率９２．８％）。得られた結晶を２０メッシュ
の篩で振るったところその９６％が篩をパスした。また
反応装置の壁および撹拌機等に付着して反応装置から取
り出すことができなかった結晶の量は１．５ｇであり、
全結晶量の２．８％であった。 Example 2 50 g of O, O'-dibenzoyl-D-tartaric acid anhydride and 150 g of water were placed in the reactor of Example 1 and the mixture was stirred at 90 to 95 ° C. for 1 hour.
It was hydrolyzed by stirring for a time. The reaction solution was cooled to 50 ° C., 5 g of toluene and 0.1 g of seed crystals of O, O′-dibenzoyl-D-tartaric acid were added, and the mixture was gradually cooled. 48 ° C
At this point, the oily substance began to crystallize, so stirring was continued for 1 hour while maintaining the temperature. After the crystallization was completely completed, the reaction slurry was cooled to room temperature and the crystals were separated by filtration. The cake obtained was dried to obtain 51.2 g of white crystals of O, O'-dibenzoyl-D-tartaric acid hydrate. The water of crystallization was 4.6% as measured by the Karl Fischer method. (Yield 92.8%). When the obtained crystals were shaken with a 20-mesh sieve, 96% thereof passed through the sieve. In addition, the amount of crystals that could not be taken out from the reaction device by adhering to the wall of the reaction device and the stirrer was 1.5 g,
It was 2.8% of the total crystal amount.
【００２０】実施例３ 実施例１の反応器にＯ，Ｏ´−ジ−ｐ−トルオイル−Ｌ
−酒石酸無水物５０ｇと水１５０ｇおよびトルエン５ｇ
を入れ、９０〜９５℃で１時間攪拌して加水分解させ
た。反応液を６３℃まで冷却したのち、Ｏ，Ｏ´−ジ−
ｐ−トルオイル−Ｌ−酒石酸の種晶０．１ｇを加え、徐
々に冷却した。６１℃に於いて油状物が結晶化し始めた
のでその温度を維持したまま１時間攪拌を続けた。結晶
化が完全に終了したのち反応スラリ−を室温まで冷却
し、結晶を濾別した。得られたケ−クを乾燥して白色結
晶のＯ，Ｏ´−ジ−ｐ−トルオイル−Ｌ−酒石酸水和物
５２．８ｇを得た。結晶水をカ−ルフィッシャ−法で測
定したところ４．５％であった。（収率９６．１％）。
得られた結晶を２０メッシュの篩で振るったところその
９８％が篩をパスした。また反応装置の壁および撹拌機
等に付着して反応装置から取り出すことができなかった
結晶の量は１．１ｇであり、全結晶量の２．０％であっ
た。 Example 3 The reactor of Example 1 was charged with O, O'-di-p-toluoyl-L.
-50 g tartaric anhydride, 150 g water and 5 g toluene.
Was added, and the mixture was stirred at 90 to 95 ° C. for 1 hour for hydrolysis. After cooling the reaction solution to 63 ° C., O, O′-di-
0.1 g of seed crystals of p-toluoyl-L-tartaric acid were added, and the mixture was gradually cooled. At 61 ° C., an oily substance began to crystallize, so stirring was continued for 1 hour while maintaining the temperature. After the crystallization was completely completed, the reaction slurry was cooled to room temperature and the crystals were separated by filtration. The cake obtained was dried to obtain 52.8 g of O, O'-di-p-toluoyl-L-tartaric acid hydrate as white crystals. It was 4.5% when the water of crystallization was measured by the Karl Fisher method. (Yield 96.1%).
When the obtained crystals were shaken with a 20-mesh sieve, 98% thereof passed through the sieve. In addition, the amount of crystals that could not be taken out from the reaction device by adhering to the walls of the reaction device and the stirrer was 1.1 g, which was 2.0% of the total amount of crystals.
【００２１】実施例４ 実施例１の反応器にＯ，Ｏ´−ジ（３，４−ジメチルベ
ンゾイル）−Ｌ−酒石酸無水物５０ｇと水１５０ｇを入
れ、９０〜９５℃で１時間攪拌して加水分解させた。反
応液を６３ ℃まで冷却してトルエン５ｇとＯ，Ｏ´−
ジ（３，４−ジメチルベンゾイル）−Ｌ−酒石酸の種晶
０．１ｇを加えたのち徐々に冷却した。６０℃に於いて
油状物が結晶化し始めたのでその温度を維持したまま１
時間攪拌を続けた。結晶化が完全に終了したのち反応ス
ラリ−を室温まで冷却し、結晶を濾別した。得られたケ
−クを乾燥して白色結晶のＯ，Ｏ´−ジ（３，４−ジメ
チルベンゾイル）−Ｌ−酒石酸水和物５２．１ｇを得
た。結晶水をカ−ルフィッシャ−法で測定したところ
３．８％であった。（収率９５．９％）。得られた結晶
を２０メッシュの篩で振るったところその９６％が篩を
パスした。また反応装置の壁および撹拌機等に付着して
反応装置から取り出すことができなかった結晶の量は
１．３ｇであり、全結晶量の２．４％であった。 Example 4 50 g of O, O'-di (3,4-dimethylbenzoyl) -L-tartaric acid anhydride and 150 g of water were placed in the reactor of Example 1 and stirred at 90 to 95 ° C. for 1 hour. It was hydrolyzed. The reaction solution was cooled to 63 ° C., and 5 g of toluene and O, O′-
After seeding with 0.1 g of di (3,4-dimethylbenzoyl) -L-tartaric acid, the mixture was gradually cooled. At 60 ° C, oil began to crystallize, so while maintaining that temperature 1
Stirring was continued for hours. After the crystallization was completely completed, the reaction slurry was cooled to room temperature and the crystals were separated by filtration. The cake thus obtained was dried to obtain 52.1 g of O, O'-di (3,4-dimethylbenzoyl) -L-tartaric acid hydrate as white crystals. The water of crystallization was 3.8% as measured by the Cal-Fisher method. (Yield 95.9%). When the obtained crystals were shaken with a 20-mesh sieve, 96% thereof passed through the sieve. The amount of crystals attached to the wall of the reactor and the stirrer and the like could not be taken out from the reactor was 1.3 g, which was 2.4% of the total amount of crystals.
【００２２】実施例５ 実施例１の反応器にＯ，Ｏ´−ジ（２−クロロベンゾイ
ル）−Ｌ−酒石酸無水物５０ｇと水１５０ｇを入れ、９
０〜９５℃で１時間攪拌して加水分解させた。反応液を
４３℃まで冷却してトルエン５ｇとＯ，Ｏ´−ジ（２−
クロロベンゾイル）−Ｌ−酒石酸の種晶０．１ｇを加え
たのち徐々に冷却した。３９℃に於いて油状物が結晶化
し始めたのでその温度を維持したまま１時間攪拌を続け
た。結晶化が完全に終了したのち反応スラリ−を室温ま
で冷却し、結晶を濾別した。得られたケ−クを乾燥して
白色結晶のＯ，Ｏ´−ジ（２−クロロベンゾイル）−Ｌ
−酒石酸水和物５１．７ｇを得た。結晶水をカ−ルフィ
ッシャ−法で測定したところ４．８％であった。（収率
９４．３％）。得られた結晶を２０メッシュの篩で振る
ったところその９５％が篩をパスした。また反応装置の
壁および撹拌機等に付着して反応装置から取り出すこと
ができなかった結晶の量は１．９ｇであり、全結晶量の
３．５％であった。 Example 5 The reactor of Example 1 was charged with 50 g of O, O'-di (2-chlorobenzoyl) -L-tartaric acid anhydride and 150 g of water.
It was hydrolyzed by stirring at 0 to 95 ° C for 1 hour. The reaction solution was cooled to 43 ° C., and 5 g of toluene and O, O′-di (2-
After adding 0.1 g of seed crystals of chlorobenzoyl) -L-tartaric acid, the mixture was gradually cooled. At 39 ° C., an oily substance began to crystallize, so stirring was continued for 1 hour while maintaining the temperature. After the crystallization was completely completed, the reaction slurry was cooled to room temperature and the crystals were separated by filtration. The cake obtained was dried to give white crystals of O, O'-di (2-chlorobenzoyl) -L.
51.7 g of tartaric acid hydrate were obtained. It was 4.8% when the water of crystallization was measured by the Cal-Fisher method. (Yield 94.3%). When the obtained crystals were shaken with a 20-mesh sieve, 95% thereof passed through the sieve. The amount of crystals that could not be taken out from the reaction device by adhering to the walls of the reaction device and the stirrer was 1.9 g, which was 3.5% of the total amount of crystals.
【００２３】[0023]
【発明の効果】本発明によれば、Ｏ，Ｏ´−ジアシル酒
石酸無水物を加水分解させてＯ，Ｏ´−ジアシル酒石酸
の結晶を得る際、水と混和しない有機溶媒を共存させる
ことにより、塊状物を生成させることなく操作性良く高
収率でＯ，Ｏ´−ジアシル酒石酸の結晶を製造すること
ができる。According to the present invention, when O, O'-diacyltartaric acid anhydride is hydrolyzed to obtain O, O'-diacyltartaric acid crystals, an organic solvent immiscible with water is allowed to coexist. O, O'-diacyltartaric acid crystals can be produced in good yield with good operability without producing lumps.
Claims (3)
数１〜３のアルキル基を示し、Ｒ1 、Ｒ2 が同一でも、
異なっても良い。）で示される化合物を水中で加水分解
して下記一般式（II） 【化２】 （式中Ｒ1 、Ｒ2 は一般式（Ｉ）のＲ1 、Ｒ2 と同じも
のであり、水素原子、ハロゲン原子或いは炭素数１〜３
のアルキル基を示す。）で示される化合物を得るに際
し、水と混和しない有機溶媒を共存させることを特徴と
する一般式（II）で示されるＯ，Ｏ´−ジアシル酒石酸
の製造方法。1. The following general formula (I): (In the formula, R 1 and R 2 represent a hydrogen atom, a halogen atom or an alkyl group having 1 to 3 carbon atoms, and even if R 1 and R 2 are the same,
It can be different. ) Is hydrolyzed in water to give a compound represented by the following general formula (II): (Are those same as R 1, R 2 in the formula R 1, R 2 is the formula (I), a hydrogen atom, a halogen atom or 1 to 3 carbon atoms
Is an alkyl group. ) A method for producing O, O'-diacyltartaric acid represented by the general formula (II), characterized in that an organic solvent immiscible with water is allowed to coexist when obtaining the compound represented by the formula (1).
される化合物に対して０．０１乃至０．５倍重量である
請求項１の記載の製造方法。2. The production method according to claim 1, wherein the amount of the organic solvent added is 0.01 to 0.5 times the weight of the compound represented by the general formula (I).
キシレン又はクロロベンゼンである請求項１の記載の製
造方法。3. The organic solvent added is benzene, toluene,
The production method according to claim 1, which is xylene or chlorobenzene.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP31453093A JP3208971B2 (en) | 1993-11-19 | 1993-11-19 | Process for producing O, O'-diacyltartaric acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP31453093A JP3208971B2 (en) | 1993-11-19 | 1993-11-19 | Process for producing O, O'-diacyltartaric acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH07138206A true JPH07138206A (en) | 1995-05-30 |
| JP3208971B2 JP3208971B2 (en) | 2001-09-17 |
Family
ID=18054401
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP31453093A Expired - Fee Related JP3208971B2 (en) | 1993-11-19 | 1993-11-19 | Process for producing O, O'-diacyltartaric acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3208971B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006050633A1 (en) * | 2004-11-11 | 2006-05-18 | Institute Of Pharmacology And Toxicology Academy Of Military Medical Sciences P.L.A. China | The process for resolving dl-ephedrine or the derivatives thereof and the resolving agents |
| WO2006056098A1 (en) * | 2004-11-23 | 2006-06-01 | Institute Of Pharmacology And Toxicology Academy Of Military Medical Sciences P.L.A. China | The process for resolving dl-epherine, pseudoephedrine or the derivatives thereof and the resolving agents |
| CN100391932C (en) * | 2003-09-28 | 2008-06-04 | 中国人民解放军军事医学科学院毒物药物研究所 | L. (-) tartaric acid or ramification as resolving agent for resolving DL-ephedrine or ramification and resolution method |
-
1993
- 1993-11-19 JP JP31453093A patent/JP3208971B2/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100391932C (en) * | 2003-09-28 | 2008-06-04 | 中国人民解放军军事医学科学院毒物药物研究所 | L. (-) tartaric acid or ramification as resolving agent for resolving DL-ephedrine or ramification and resolution method |
| WO2006050633A1 (en) * | 2004-11-11 | 2006-05-18 | Institute Of Pharmacology And Toxicology Academy Of Military Medical Sciences P.L.A. China | The process for resolving dl-ephedrine or the derivatives thereof and the resolving agents |
| WO2006056098A1 (en) * | 2004-11-23 | 2006-06-01 | Institute Of Pharmacology And Toxicology Academy Of Military Medical Sciences P.L.A. China | The process for resolving dl-epherine, pseudoephedrine or the derivatives thereof and the resolving agents |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3208971B2 (en) | 2001-09-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4659838A (en) | Method of resolving bicyclic imino-α-carboxylic acid ester racemates | |
| JP2604333B2 (en) | Novel λ-modified crystal of pentaerythritol tetrakis- [3- (3,5-di-tert-butyl-4-hydroxyphenyl) propionate] and a method for producing the same | |
| JPH0684332B2 (en) | Method for optical resolution of a-isopropyl-p-chlorophenylacetic acid | |
| IE63071B1 (en) | Pharmaceutically useful polymorphic modification of buspirone | |
| JPH07138206A (en) | Production of o, o'-diacyltartaric acid | |
| US5843863A (en) | Process for improving flow characteristics of crystalline ibuprofen | |
| JPH03101668A (en) | Production of tazanolast | |
| JPH02214504A (en) | Method for depositing crystal of compound having plural crystal forms | |
| EP0105664B1 (en) | Process for the preparation of 3-carboxy-1-methylpyrrol-2-acetic-acid and alkali metal salts thereof | |
| EP0179487B1 (en) | 2-phenylpropionic acid esters, method for optical resolution thereof and optically active substance thereof | |
| JPH0840984A (en) | Method for granulating tetrakis(9146/28)3-(3',5'-di-tertiary butyl-4'-hydroxyphenyl) propionyloxymethyl(9147/28)methane | |
| EP0985658B1 (en) | Process for producing l-valine benzyl ester p-toluenesulfonate | |
| EP0018813B1 (en) | Crystalline germaazaspirodiones,their preparation and their use in the preparation of germaazaspiranes | |
| US6008413A (en) | Process for recrystallizing 1,3-bis(aminophenoxy benzene) | |
| JP3890543B2 (en) | Process for producing guanidines | |
| US4308383A (en) | N-(3-(1'-3"-Oxapentamethyleneamino-ethylideneamino)-2,4,6-triiodobenzoyl)-β-amino-α-methylpropionitrile | |
| JP2857037B2 (en) | Method for crystallizing N-alkoxycarbonyl amino acid ester | |
| JPH0249752A (en) | Method for crystallizing and purifying beta-crystal of tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionyloxymethyl)methane | |
| JPH0150219B2 (en) | ||
| JPH1045752A (en) | Production of imidazole-isocyanuric acid adduct | |
| JPH02129144A (en) | Simple production of high-purity bis(2,4,6-trichlorophenyl) oxalate | |
| JPH07103115B2 (en) | Method for crystallizing 2- (10,11-dihydro-10-oxodibenzo [b, f] thiepin-2-yl) propionic acid | |
| JPH02235848A (en) | Independent granular alpha-crystal tetrakis(3-(3,5-di-tert-butyl 4-hydroxyphenyl)propionyloxymethyl)methane and production thereof | |
| JPS60166685A (en) | Non-hygroscopic adinazolum methanesulfonate | |
| JPS6242971A (en) | Production of pyrazole derivative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| FPAY | Renewal fee payment (prs date is renewal date of database) |
Year of fee payment: 8 Free format text: PAYMENT UNTIL: 20090713 |
|
| FPAY | Renewal fee payment (prs date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20100713 Year of fee payment: 9 |
|
| FPAY | Renewal fee payment (prs date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110713 Year of fee payment: 10 |
|
| LAPS | Cancellation because of no payment of annual fees |